Reated sufferers (Data Supplement). A planned interim evaluation of OS was carried out, like 96 (44 ) from the 217 patient Dopamine Transporter drug deaths needed for the final analysis. In thisjco.organalysis, no statistically significant distinction involving remedy arms was observed (HR, 0.98; 95 CI, 0.63 to 1.52). Survival follow-up is planned to continue until at least 217 deaths have been observed. Calcitonin and CEA Calcitonin and CEA response at week 12 was evaluable in 140 (64 ) and 170 (78 ) cabozantinib-treated individuals and 61 (55 ) and 71 (64 ) placebo-treated patients, respectively. Probably the most frequent factors patients had been not evaluable have been the lack of a week-12 assessment or maybe a calcitonin assay alter among the baseline and week-12 assessments (information are provided inside the Data Supplement). At baseline, the imply value and normal deviation (SD) for calcitonin in the cabozantinib and placebo arms were 6,370 pmol/L (SD, 11,332 pmol/L) and eight,846 pmol/L (SD, 15,722 pmol/L), respectively (Welsh’s t test P .27). For CEA, the mean values for cabozantinib and placebo arms have been 736 g/L (SD, 3,555 g/L) and 1,108 g/L (SD, five,168 g/L), respectively (Welsh’s t test P .58). These baseline values have been judged to become not meaningfully unique. From baseline to week 12, the cabozantinib arm displayed significant decreases in calcitonin (mean, 45.two [SD, 60.71 ]) compared with increases within the placebo arm ( 57.three ; SD, 115.4 ; P .001). Changes in CEA levels from baseline to week 12 showed a equivalent trend ( 23.7 [SD, 58.21 ] inside the cabozantinib arm v 88.7 [SD, 182. ] within the placebo arm; P .001. A normally linear connection was observed when changes in calcitonin and CEA from baseline to week 12 (as much as roughly 200 increases) had been compared with modifications in SIRT3 Purity & Documentation target lesion size (Fig 3). Safety and Tolerability AEs reported in 10 of cabozantinib-treated patients are summarized in Table 2. Grade three or 4 AEs were reported in 69 (148 of 214) and 33 (36 of 109) of individuals in the cabozantinib and placebo groups, respectively. In cabozantinib-treated individuals, probably the most regularly reported grade 3 or four AEs have been diarrhea (15.9 ), palmarplantar erythrodysesthesia (12.6 ), and fatigue (9.3 ). AEs generally?2013 by American Society of Clinical OncologyElisei et alTable 1. Baseline Demographic and Disease Characteristics Cabozantinib (n 219) Characteristic Male sex Age, years Median Variety 65 65 ECOG PS 0 1-2 RET mutation status Optimistic Unfavorable Unknown MTC disease type Hereditary Sporadic Unknown RET M918T mutation status Positive Damaging Unknown Sufferers with prior anticancer therapy Patients with prior systemic therapy for MTC Individuals with two or more prior systemic therapies Individuals with prior thyroidectomy Prior TKI status Yes Vandetanib Sorafenib Motesanib Sunitinib No Unknown No. of organs and anatomic locations involved at enrollment 0-1 2 Major web sites of metastatic disease Lymph nodes Liver Lung Bone No. 151 68.9 Placebo (n 111) No. 70 63.55.0 20-86 172 78.5 47 21.five 123 95 101 31 87 12 191 16 75 67 77 85 81 52 201 44 25 11 7 six 171 four 56.two 43.four 46.1 14.two 39.7 five.5 87.2 7.3 34.two 30.six 35.2 38.eight 37.0 23.7 91.8 20.1 11.four 5.0 three.two 2.7 78.1 1.55.0 21-79 86 77.5 25 22.5 56 55 58 ten 43 eight 94 9 43 30 38 48 47 31 104 24 9 eight two three 86 1 50.5 49.5 52.3 9.0 38.7 7.2 84.7 eight.1 38.7 27.0 34.2 43.two 42.three 27.9 93.7 21.six eight.1 7.2 1.eight 2.7 77.five 0.28 191 175 152 11612.eight 87.two 79.9 69.four 53.0 51.15 96 86 67 6413.five 86.five 77.five 60.4 57.7 50.Abbreviations: ECOG PS, Eastern Cooperative Oncology Group.